Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, NorwayAuthors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, NorwayAuthors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, NorwayAuthors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, NorwayAuthors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, NorwayAuthors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Authors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, NorwayAuthors' Affiliations: Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Department of Gastrointestinal Surgery, Aker University Hospital, Oslo University Hospital; Centre for Cancer Biomedicine, Faculty of Medicine, Department of Informatics, University of Oslo; Department of Forensic Pathology And Clinical Forensic Medicine, Division for Forensic Medicine, The Norwegian Institute of Public Health, Oslo; and Akershus University Hospital, University of Oslo, Research Centre, Lørenskog, Norway

Abstract

Purpose: Improved prognostic stratification of patients with stage II and III colorectal cancer is warranted for postoperative clinical decision making. This study was conducted to develop a clinically feasible and robust prognostic classifier for these patients independent of adjuvant treatment.

Experimental Design: Global gene expression profiles from altogether 387 stage II and III colorectal cancer tissue samples from three independent patient series were included in the study. ColoGuidePro, a seven-gene prognostic classifier, was developed from a selected Norwegian learning series (n = 95; no adjuvant treatment) using lasso-penalized multivariate survival modeling with cross-validation.

Results: The expression signature significantly stratified patients in a consecutive Norwegian test series, in which patients were treated according to current standards [HR, 2.9 (1.1–7.5); P = 0.03; n = 77] and an external validation series [HR, 3.7 (2.0–6.8); P < 0.001; n = 215] according to survival. ColoGuidePro was also an independent predictor of prognosis in multivariate models including tumor stage in both series (HR, ≥3.1; P ≤ 0.03). In the validation series, which consisted of patients from other populations (United States and Australia), 5-year relapse-free survival was significantly predicted for stage III patients only (P < 0.001; n = 107). Here, prognostic stratification was independent of adjuvant treatment (P = 0.001).